ClinVar Miner

Submissions for variant NM_000304.4(PMP22):c.469C>T (p.Arg157Trp)

dbSNP: rs28936682
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics Laboratory, London Health Sciences Centre RCV001173916 SCV001337034 likely pathogenic Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001229968 SCV001402432 pathogenic Charcot-Marie-Tooth disease, type I 2025-01-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 157 of the PMP22 protein (p.Arg157Trp). This variant is present in population databases (rs28936682, gnomAD 0.0009%). This missense change has been observed in individuals with autosomal recessive Dejerine-Sottas disease (PMID: 10211478, 32719652). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 8444). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt PMP22 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV001332355 SCV001524655 likely pathogenic Hereditary liability to pressure palsies 2020-08-04 criteria provided, single submitter clinical testing This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Illumina Laboratory Services, Illumina RCV001229968 SCV005431536 pathogenic Charcot-Marie-Tooth disease, type I 2024-11-22 criteria provided, single submitter clinical testing The PMP22 c.469C>T p.(Arg157Trp) missense variant has been identified in trans with a pathogenic variant in individuals with a phenotype consistent with Charcot-Marie-Tooth disease. This variant has been shown to segregate with disease (PMID: 10211478; 32719652). This variant is not observed at a significant frequency in version 4.1.0 of the Genome Aggregation Database. Multiple lines of computational evidence suggest the variant may impact the gene or gene product. This variant has been classified as likely pathogenic or pathogenic by multiple submitters in ClinVar. Based on the evidence, the c.469C>T p.(Arg157Trp) variant has been classified as pathogenic for Charcot-Marie-Tooth disease.
OMIM RCV000008957 SCV000029169 pathogenic Autosomal recessive Dejerine-Sottas syndrome 1999-04-01 no assertion criteria provided literature only
GeneReviews RCV000193053 SCV000243949 not provided Charcot-Marie-Tooth disease type 1E no assertion provided literature only

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